tbuckley/cabot-search huggingface dataset:
Evaluation of the state of colonic microflora in patients with non-alcoholic fatty liver disease with immune response to SARS-CoV-2
Authors: Yu.M. Stepanov, V.I. Didenko, I.A. Klenina, O.M. Tatarchuk, N.S. Vishnarevska, O.P. Petishko
Journal: GASTROENTEROLOGY (2023)

Background. The prevalence of non-alcoholic fatty liver disease (NAFLD) is currently increasing worldwide and is a serious problem that causes interest in its study, especially in patients with an immune response to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). In recent years, studies have been investigating the influence of microflora on the development and progression of NAFLD. The purpose of the study was to determine the level of dysbiotic disorders of the colonic microbiocenosis in patients with NAFLD with an immune response to SARS-CoV-2. Materials and methods. We examined 34 patients with NAFLD who were found to have IgG to SARS-CoV-2. All examined patients were divided into two groups: group I consisted of 17 patients with no history of SARS-CoV-2 according to the polymerase chain reaction (PCR) data; group II— 17 patients with a history of SARS-CoV-2 by PCR. The control group consisted of 10 practically healthy individuals. Chromatographic determination of the content of short-chain fatty acids, species and quantitative composition of the colonic microflora was performed. Results. The microbiological studies revealed changes in the qualitative and quantitative composition of the colonic microflora in 88.2% of patients with NAFLD, with a predominance of dysbiosis II in 41.2% of patients in group I and dysbiosis I in 70.6% of patients in group II. These changes were due to a decrease in the number of bifidobacteria and lactobacilli, an increase in the concentration of opportunistic pathogens, fungi of the genus Candida spp. The intestinal microbiome of patients with NAFLD who had SARS-CoV-2 showed impaired biosynthesis of short-chain fatty acids in the coprofiltrate, which was manifested by an increase in the median acetic and propionic acids and a decrease in the median butyric acid in patients of group I. The median anaerobic index had a statistically significant decrease in patients of group I by 1.5 times (p&lt;0.05) and a tendency to a decrease in patients of group II. Significant intergroup differences were found for anaerobic index, its median was 1.4 times higher in group II (p&lt;0.05) compared with group I. Conclusions. A decrease in the level of normoflora representatives, an increase in opportunistic pathogens, a tendency to a decrease in the concentration of butyric acid, an increase in acetic and propionic acids in the feces were found in patients with NAFLD who had SARS-CoV-2.
The relationship between body weight and the development of lipid and carbohydrate metabolism disorders in patients with gastrointestinal diseases
Authors: Yu.M. Stepanov, L.M. Mosiychuk, O.M. Shevtsova, I.A. Klenina, V.A. Karachynova, O.M. Tatarchuk, O.P. Petishko
Journal: GASTROENTEROLOGY (2023)

Background. The purpose of the study is to investigate the peculiarities of lipid and carbohydrate metabolism in patients with gastrointestinal diseases depending on the body mass index (BMI). Materials and methods. Forty patients with digestive disorders were examined, 13 women (32.5%) and 27 men (67.5%) whose median age was 37 (24; 51) years. The patients were divided into 3 groups: I— 20 people with BMI exceeding the norm; II— 11 patients with a BMI below the norm; III— 9 patients with normal BMI. The control group for evaluating the results of laboratory tests consisted of 15 practically healthy people. Total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), glucose and insulin serum levels were evaluated. The atherogenic index (AI) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were calculated. Statistical processing of the results was carried out using the Statistica 6.1 software package. Results. In patients with digestive diseases who had an increased BMI, the development of atherogenic dyslipidemia was detected, as indicated by a probable decrease in serum content of HDL-C by 1.7 times (p=0.003) and an increase in TG by 1.9 times (p=0.002), VLDL-C by 1.4 times (p=0.05), AI by 2 times (p=0.03) compared to the controls. No significant signs of the development of atherosclerotic processes were found in patients with reduced and normal BMI. Carbohydrate metabolism disorders were observed in 47.5% of patients with gastrointestinal diseases, and HOMA-IR in patients with increased BMI was 2.9 times higher (p&lt;0.05) compared to those with reduced BMI and 2.5 times (p&lt;0.05) higher— with normal BMI. It was found that an increase in BMI is associated with an increase in serum TG (r=0.381; p=0.017), LDL-С (r=0.383; p=0.016), AI (r=0.566; p&lt;0.001), insulin (r=0.651; p=0.0001) and HOMA-IR (r=0.681; p=0.0001), as well as that BMI is negatively correlated with the content of HDL-С (r=–0.448; p=0.004). At the same time, an inverse correlation was found between HOMA-IR and the level of HDL-С (r= –0.389; p=0.016), and a direct relationship between the index of insulin resistance and AI (r=0.437; p=0.006). Conclusions. The revealed correlations confirm the hypothesis of the BMI influence on the development of dyslipidemia and insulin resistance in patients with gastrointestinal diseases. This substantiates the expediency of including bioimpedance measurements into the algorithm for predicting metabolic disorders in this category of patients.
Xanthomas and precancerous changes of the stomach: an accidental combination or an important prognostic endoscopic marker?
Authors: O.V. Simonova, L.M. Mosiychuk, O.P. Petishko
Journal: GASTROENTEROLOGY (2023)

Background. The article deals with the study of gastric xanthomas, benign accidental formations with an unknown etiopathogenesis, which, according to the literature, are associated with a number of pathological conditions (atrophic gastritis, intestinal metaplasia, dysplasia, gastric cancer, dyslipidemia, etc.). The purpose was to study the prevalence of gastric xanthomas in patients with atrophic gastritis and to analyze their relationship with endoscopic changes in the stomach, including precancerous conditions. Materials and methods. Esophagogastroduodenoscopy was performed using the EVIS EXERA III video endoscopy system with the Olympus 190 gastroscope (Japan) in 120 patients with atrophic gastritis undergoing examination and treatment at the Institute of Gastroenterology of the National Academy of Sciences of Ukraine. The presence of duodenogastric reflux, the prevalence and severity of mucosal atrophy, changes in the relief of the gastric mucosa (including nodules and bumps), the presence of hyperplasia, polyps, hemorrhages, erosions, ulcers, xanthomas in the stomach were assessed. When using the narrow-band imaging and close focus, the presence and prevalence of intestinal metaplasia, the presence of gastric dysplasia were evaluated. Comparative and statistical analysis of endoscopic data was conducted depending on the presence of gastric xanthomas. Results. The heterogeneity of endoscopic changes in atrophic gastritis was revealed (prevalence and severity of atrophy, intestinal metaplasia, changes in the mucosal relief, presence of hyperplasia, polyps, ulcers, etc.). Gastric xanthomas were found in more than a third of patients with atrophic gastritis (36.7 % of cases), with predominant localization in the antral region (90.9 %). As a rule (95.5 %), they were single. In patients with atrophic gastritis associated with xanthomas, diffuse atrophic changes in gastric mucosa were detected significantly more often, as well as mucosal nodules and bumps, mucosal hyperplasia, intestinal metaplasia and the mucosal dysplasia, which was confirmed morphologically (p &lt; 0.05). Rare cases of gastric ulcers and gastric cancer were diagnosed only in patients with xanthomas (p &gt; 0.05). Conclusions. The obtained results indicate that gastric xanthoma is an important diagnostic marker of precancerous changes in the gastric mucosa: widespread atrophy, intestinal metaplasia, dysplasia, and can be used as an important prognostic marker for the development of gastric cancer. Patients with xanthoma-associated atrophic gastritis require a thorough examination using modern endoscopic equipment and dynamic observation, with a focus on changes in the gastric relief by the type of nodules and bumps.
A clinical case of acute anabolic steroid-induced toxic hepatitis
Authors: L.V. Demeshkina, V.B. Yagmur, S.L. Melanich, D.V. Popok
Journal: GASTROENTEROLOGY (2023)

Drug-induced liver injury (DILI) can be considered in cases of acute hepatitis by the exclusion of any disease-related causes. For several decades, anabolic steroids have been considered not only as drugs for treatment of diseases such as hypogonadism, sarcopenia, hypotrophy in cancer patients, aplastic anemia, etc., but also as risk factor for acute liver failure, that can lead to liver cancer, and even sudden death. Anabolic steroids are known to be increasingly used not only for legitimate medical uses, but also for enhance physical performance and promote muscle growth for ideal body shape. The article presents a clinical case of acute drug-induced hepatitis after 2 months of using stanozolol, a synthetic testosterone derivative, in a 25-year-old previously healthy man. Thorough etiological investigations ruled out other causes of DILI. The man was treated at the in-patient department and discharged with improvement, but it took several months for the disappearance of hepatic cytolytic and cholestatic changes. Clinicians should be aware of the risk for toxic drug-induced hepatitis in male bodybuilders and collect a thorough history of the patient’s intake of nutritional supplements that may contain androgen derivatives.
Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies
Authors: Ariella Glasner, Samuel A. Rose, Roshan Sharma, Herman Gudjonson, Tinyi Chu, Jesse A. Green, Sham Rampersaud, Izabella K. Valdez, Emma S. Andretta, Bahawar S. Dhillon, Michail Schizas, Stanislav Dikiy, Alejandra Mendoza, Wei Hu, Zhong-Min Wang, Ojasvi Chaudhary, Tianhao Xu, Linas Mazutis, Gabrielle Rizzuto, Alvaro Quintanal-Villalonga, Parvathy Manoj, Elisa de Stanchina, Charles M. Rudin, Dana Pe’er, Alexander Y. Rudensky
Journal: Nature Immunology (2023)

Abstract While regulatory T (T reg ) cells are traditionally viewed as professional suppressors of antigen presenting cells and effector T cells in both autoimmunity and cancer, recent findings of distinct T reg cell functions in tissue maintenance suggest that their regulatory purview extends to a wider range of cells and is broader than previously assumed. To elucidate tumoral T reg cell ‘connectivity’ to diverse tumor-supporting accessory cell types, we explored immediate early changes in their single-cell transcriptomes upon punctual T reg cell depletion in experimental lung cancer and injury-induced inflammation. Before any notable T cell activation and inflammation, fibroblasts, endothelial and myeloid cells exhibited pronounced changes in their gene expression in both cancer and injury settings. Factor analysis revealed shared T reg cell-dependent gene programs, foremost, prominent upregulation of VEGF and CCR2 signaling-related genes upon T reg cell deprivation in either setting, as well as in T reg cell-poor versus T reg cell-rich human lung adenocarcinomas. Accordingly, punctual T reg cell depletion combined with short-term VEGF blockade showed markedly improved control of PD-1 blockade-resistant lung adenocarcinoma progression in mice compared to the corresponding monotherapies, highlighting a promising factor-based querying approach to elucidating new rational combination treatments of solid organ cancers.
Endoscopic features of the intestinal mucosa in patients with ulcerative colitis depending on the level of IgG4
Authors: Yu.M. Stepanov, M.V. Stoykevich, Yu.A. Gaidar, T.S. Tarasova, O.V. Simonova, O.M. Tatarchuk, O.P. Petishko
Journal: GASTROENTEROLOGY (2023)

Background. Ulcerative colitis has long-term severe local and systemic consequences, often recurs which determines the urgency of developing new diagnostic markers for screening this pathology. The purpose of the study: to investigate the endoscopic picture of the colonic mucosa in ulcerative colitis depending on the content of IgG4 in the blood serum and the presence of tissue IgG4. Materials and methods. Seventy-five patients with ulcerative colitis were examined, they were treated at the department of intestinal diseases of the State Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”. Of them, 42 were women and 33 were men aged 18 to 69 years, the average age was (40.1±1.4) years. Most patients (n=54) had a moderate ulcerative colitis, in 14 patients, the course was severe and 7 people had a mild ulcerative colitis. Endoscopic studies of the colon were performed according to generally accepted methods using the video colonoscope Olympus EVIS EXERA III (Japan). The level of IgG4 in blood serum was evaluated in all patients using the Stat Fax 303 Plus immunoassay analyzer (USA) according to the instructions for the test kit of reagents manufactured by the Xema company (Ukraine). The control group consisted of 15 practically healthy people. The presence of IgG4-positive plasma cells was determined by the immunohistochemical method, using monoclonal rabbit anti-human IgG4 (Abcam, USA). Results. An increase in the level of IgG4 over 1.2 g/l was detected in 45 patients. In general, in patients with ulcerative colitis the concentration of IgG4 in blood serum was 2 times higher (p&lt;0.05) compared to the control group: 1.50 (0.55; 2.25) g/l versus 0.65 (0.45; 0.80) g/l. Patients with ulcerative colitis had an increase in the level of both serum and tissue IgG4 accompanied by an increase in the frequency of detecting the endoscopic signs of the disease; therefore, endoscopic activity of degree 3 is detected 2 times (p&lt;0.05) and 2.9 times (p&lt;0.001) more often than in patients with normal concentration of IgG4. Conclusions. Correlations found between the levels of serum and tissue IgG4, as well as with the severity of endoscopic manifestations of ulcerative colitis substantiate the feasibility of assessing the level of IgG4 in the blood as a non-invasive marker for predicting the course of this disease.
Effects of different doses of exercise and diet-induced weight loss on beta-cell function in type 2 diabetes (DOSE-EX): a randomized clinical trial
Authors: Grit E. Legaard, Mark P. P. Lyngbæk, Thomas P. Almdal, Kristian Karstoft, Sebastian L. Bennetsen, Camilla S. Feineis, Nina S. Nielsen, Cody G. Durrer, Benedikte Liebetrau, Ulrikke Nystrup, Martin Østergaard, Katja Thomsen, Beckey Trinh, Thomas P. J. Solomon, Gerrit Van Hall, Jan Christian Brønd, Jens J. Holst, Bolette Hartmann, Robin Christensen, Bente K. Pedersen, Mathias Ried-Larsen
Journal: Nature Metabolism (2023)

Diet-induced weight loss is associated with improved beta-cell function in people with type 2 diabetes (T2D) with remaining secretory capacity. It is unknown if adding exercise to diet-induced weight loss improves beta-cell function and if exercise volume is important for improving beta-cell function in this context. Here, we carried out a four-armed randomized trial with a total of 82 persons (35% females, mean age (s.d.) of 58.2 years (9.8)) with newly diagnosed T2D (<7 years). Participants were randomly allocated to standard care (n = 20), calorie restriction (25% energy reduction; n = 21), calorie restriction and exercise three times per week (n = 20), or calorie restriction and exercise six times per week (n = 21) for 16 weeks. The primary outcome was beta-cell function as indicated by the late-phase disposition index (insulin secretion multiplied by insulin sensitivity) at steady-state hyperglycemia during a hyperglycemic clamp. Secondary outcomes included glucose-stimulated insulin secretion and sensitivity as well as the disposition, insulin sensitivity, and secretion indices derived from a liquid mixed meal tolerance test. We show that the late-phase disposition index during the clamp increases more in all three intervention groups than in standard care (diet control group, 58%; 95% confidence interval (CI), 16 to 116; moderate exercise dose group, 105%; 95% CI, 49 to 182; high exercise dose group, 137%; 95% CI, 73 to 225) and follows a linear dose-response relationship (P > 0.001 for trend). We report three serious adverse events (two in the control group and one in the diet control group), as well as adverse events in two participants in the diet control group, and five participants each in the moderate and high exercise dose groups. Overall, adding an exercise intervention to diet-induced weight loss improves glucose-stimulated beta-cell function in people with newly diagnosed T2D in an exercise dose-dependent manner (NCT03769883).
M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer’s patch
Authors: Natalia Torow, Ronghui Li, Thomas Charles Adrian Hitch, Clemens Mingels, Shahed Al Bounny, Niels van Best, Eva-Lena Stange, Britta Simons, Tiago Maié, Lennart Rüttger, Narasimha Murthy Keshava Prasad Gubbi, Darryl Adelaide Abbott, Adam Benabid, Michael Gadermayr, Solveig Runge, Nicole Treichel, Dorit Merhof, Stephan Patrick Rosshart, Nico Jehmlich, Timothy Wesley Hand, Martin von Bergen, Felix Heymann, Oliver Pabst, Thomas Clavel, Frank Tacke, Hugues Lelouard, Ivan Gesteira Costa, Mathias Walter Hornef
Journal: Immunity (2023)

Early-life immune development is critical to long-term host health. However, the mechanisms that determine the pace of postnatal immune maturation are not fully resolved. Here, we analyzed mononuclear phagocytes (MNPs) in small intestinal Peyer's patches (PPs), the primary inductive site of intestinal immunity. Conventional type 1 and 2 dendritic cells (cDC1 and cDC2) and RORgt+ antigen-presenting cells (RORgt+ APC) exhibited significant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, subsequently resulting in a lack in CD4+ T cell priming during the postnatal period. Microbial cues contributed but could not fully explain the discrepancies in MNP maturation. Type I interferon (IFN) accelerated MNP maturation but IFN signaling did not represent the physiological stimulus. Instead, follicle-associated epithelium (FAE) M cell differentiation was required and sufficient to drive postweaning PP MNP maturation. Together, our results highlight the role of FAE M cell differentiation and MNP maturation in postnatal immune development.
Excessive Brain Volume Loss Over Time in Cannabis-Using First-Episode Schizophrenia Patients
Authors: Monica Rais, Wiepke Cahn, Neeltje Van Haren, Hugo Schnack, Esther Caspers, Hilleke Hulshoff Pol, René Kahn
Journal: American Journal of Psychiatry (2008)

Objective: Cerebral gray matter volume reductions have been found to progress over time in schizophrenia, with larger decreases related to poorer outcome, which has also been associated with cannabis use in schizophrenia patients. Progressive gray matter changes in patients who use cannabis may be more extensive than in those who do not. Method: Patients with recent-onset schizophrenia (N=51) and matched healthy subjects (N=31) were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion (T0) and at 5-year follow-up (T5). Nineteen patients used cannabis but no other illicit drugs; 32 patients did not use any drugs during the 5-year follow-up. At T5, clinical outcome was measured. Cumulative amount of antipsychotic medication during the interval was calculated. At T0 and T5, total brain, gray and white matter, and lateral and third ventricle volumes were measured. Univariate analysis of covariance and pairwise comparisons were performed. Result: Schizophrenia patients showed a larger gray matter volume decrease over time than healthy subjects. They also showed larger increases in lateral and third ventricle volumes than healthy subjects and patients who did not use cannabis during follow-up. This decrement was significantly more pronounced in the patients who continued to use cannabis. These differences could not be attributed to outcome or baseline characteristics. Conclusions: First-episode schizophrenia patients who use cannabis show a more pronounced brain volume reduction over a 5-year follow-up than patients with schizophrenia who do not use cannabis. These results may help explain some of the detrimental effects of cannabis use in schizophrenia.
Psychotropic Drug Use in the Elderly
Authors: Jan Koch-Weser, Troy L. Thompson, Michael G. Moran, Alan S. Nies
Journal: New England Journal of Medicine (1983)

ELDERLY persons (by definition, those 65 years of age and older) now make up about 11 per cent of the U.S. population, but about 30 per cent of all prescriptions are written for this group, primarily by internists and family physicians.1 , 2 Elderly patients have a higher incidence of psychiatric disorders than younger persons and usually go first to their internist or family physician with their symptoms rather than to a psychiatrist. A disproportionately large percentage of psychotropic medications are prescribed for the elderly,3 4 5 and many older people believe that their daily performance depends on the use of such drugs.6 In . . .
Understanding Long-Term Survival of Patients with Ovarian Cancer—The Tumor Microenvironment Comes to the Forefront
Authors: Lucy Kelliher, Ernst Lengyel
Journal: Cancer Research (2023)

High-grade serous ovarian cancer (HGSOC) is the deadliest subtype of ovarian cancer, and most patients do not survive more than 5 years after diagnosis. Yet, for reasons that are often elusive, approximately 15% of women with advanced-stage HGSOC will survive longer than 10 years. An understanding of the biological basis of long-term survival with HGSOC may elucidate novel prognostic factors and targets for treatment. Past analyses of the clinicopathologic features of these women and genetic profiles of their tumors have not revealed a unifying explanation for their increased longevity. In this issue of Cancer Research, Ferri-Borgogno and colleagues investigate the tumor microenvironment (TME) in samples from both long- and short-term survivors using spatial transcriptomics and single-cell RNA sequencing. They found that, in metastatic tumors, various populations of cancer-associated fibroblasts (CAF) in the TME play different roles in supporting the malignant phenotype of ovarian cancer cells. Higher density of CAFs, particularly αSMA+VIM+PDGFRβ+ CAFs, was associated with lower tumor immune infiltration and short-term survival. There was also marked expression of periostin and CD36 in spatially resolved CAFs, as well as a prevalence of the APOE-LRP5 ligand-receptor pair at the tumor-stromal interface in tissue from short-term survivors. These findings suggest that, in short-term survivors, CAFs are able to more effectively promote tumorigenicity, stemness, and chemoresistance in the nearby tumor. See related article by Ferri-Borgogno et al., p. 1503